孕期铁营养及铁调素水平对妊娠期糖尿病发病风险的影响及机制

Iron is a very important essential element in the human body ,but too much can be harmful.Systemic iron homeostasis is maintained by the coordinate regulation of iron absorption,iron recycling, and mobilization of storage iron. Thess process are negatively controlled by hepcidin, a key iron regulatory hormone.lower hepcidin level are significantly associated with risk of iron overload and type 2 diabetes.Hepcidin level were supressed during pregnancy,which was likely to fulfill the high iron demands of pregnancy. Increased iron intake are recommanded during pregnancy as pregnant women are particularly vulnearable to iron deficency anemia.Whereas the risk of iron overload and the association with gertational diabetes mellitus (GDM) has been proposed. To reconsider the assessment of iron status and set rational guidelines for iron intake during pregnancy, we aim to obeserve iron intake from both diet and supplyment,iron status such as hemogloubine,ferritin and solubile transferri receptor, hepcidin,and inflammatory markers during pregnancy and the risk of GDM by nested case-control study within a cohort.We also explore the nutrient and gene interaction on iron status during pregnancy and the risk of GDM as where as the effects on iron storage of fetal. Animal models should be used for the undering mechanism by focus on iron intake and the hepcidin expression of liver.

铁是人体重要的必需微量元素，又有潜在的毒性作用，体内铁稳态主要依赖对铁的吸收利用及储存铁的释放进行调节。铁调素（hepcidin）对铁吸收起负性调节作用，分泌不足与铁过载和2型糖尿病有关。孕期铁需要量增加，hepcidin分泌相应减少，但铁过量也可能增加妊娠糖尿病（GDM）的风险。为精准评价孕期铁营养需要，指导铁摄入，本项目拟：（1）利用巢式病例对照研究，观察GDM和正常对照孕妇妊娠不同时期铁摄入、铁营养状况、hepcidin、氧化应激及炎性指标的动态变化及差异，分析孕期铁摄入和hepcidin水平与GDM发病风险的关系；（2）比较相关基因多态性在两组孕妇中的差异，阐明遗传因素和孕期铁摄入的交互作用对GDM发生发展的影响及其与孕妇和和胎儿铁营养的关系；（3）通过动物模型揭示孕期铁摄入对肝组织hepcidin表达和铁贮备的影响及其与GDM的关系，并探讨可能的影响机制。

铁是人体重要的必需微量元素，又有潜在的毒性作用，体内铁稳态主要依赖对铁的吸收利用及储存铁的释放进行调节。铁调素（hepcidin）对铁吸收起负性调节作用，分泌不足与铁过载和2型糖尿病有关。孕期铁需要量增加，hepcidin分泌相应减少，但铁过量也可能增加妊娠糖尿病（GDM）的风险。本项目在同济母婴队列的基础上，通过测定孕期铁蛋白、铁调素水平，分析孕期膳食及膳食补充剂铁的摄入水平、铁蛋白动态变化与GDM发病风险及胎儿生长发育和出生结局的关系。主要研究发现如下：.（1）孕早期血红蛋白水平正常的妇女，孕期长期服用含铁膳食补充剂30mg/d可显著增加GDM的风险；.（2）孕早、中期铁蛋白水平均与GDM风险呈正相关，孕早期铁蛋白中等水平（铁营养状况良好）的孕妇孕期服用高剂量铁膳食补充剂可增加GDM风险；.（3）孕期肝酶水平与GDM风险呈正相关，铁过量可能有损肝功能，从而增加GDM风险。.本项目研究提示孕期妇女应精准评估铁营养状况，谨慎服用含铁的膳食补充剂，并监测肝功能，以预防GDM，保护孕妇和胎儿的健康。